Measurements of regional cerebral blood flow (rCBF) during stimulation, and the effect of drugs which modulate synaptic function, can be used to examine synaptic integrity of the brain in health and disease. In healthy subjects performing an active working memory for faces task, rCBF effects of physostigmine, an inhibitor of acetylcholinesterase, were measured by positron emission tomography (PET) with [15-O]water. Significant effects became stable within 40 minutes after establishing a steady-state plasma concentration of physostigmine. No habituation with repeated testing was evident. Subjects performing the task had increased rCBF in occipitotemporal visual brain regions and in right prefrontal cortex. Physostigmine reduced rCBF increments in the right prefrontal cortex in relation to a decreased reaction time, indicating that the right prefrontal cortex is involved in effort. No age effect of physostigmine was evident with regard to rCBF responses and reaction time during the working memory task. The presentation of alternately flashing lights by goggles at parametrically varied frequencies evoked biphasic responses in striate cortex in control subjects. The Alzheimer's Disease (AD) group showed smaller high frequency striate rCBF response and failure to activate a mid-temporal V5 region at 1 Hz, consistent with failure of the high frequency responsive magnocellular visual system. Textured visual patterns were presented passively to healthy subjects using PET and [15-O] water Repeated visual stimulation leads to a shift of the regional rCBF response from occipital lobe to temporal and frontal lobes to hippocampus with repeated presentation, suggesting processing of complex textures. Regional cerebral metabolic rates for glucose (rCMRglc) are lower at rest in AD relative to controls in many parietal and occipital visual areas, but can be fully activated in these areas by a visual stimulus, suggesting that functional failure in AD may be reversed.